Uremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Specimen part
View SamplesDeletions at 15q11.2 have been established to increase risk for multiple neurodevelopmental disorders (NDDs) including schizophrenia and epilepsy, yet show variable expressivity between individuals. To investigate the potential role of CYFIP1, a gene within the locus, we carried out knockdown experiments in human neural progenitor cells derived from 15q11.2 neutral induced pluripotent stem cells. Transcriptional profiling and cellular assays support a prominent role for CYFIP1 in cytoskeletal remodeling across all lines examined. Validating the utility of this model for study of disease, genes implicated in schizophrenia and epilepsy but not other disorders or traits unrelated to the deletion, were enriched among mRNAs dysregulated following knockdown. Importantly, and consistent with the variable expressivity of 15q11.2 deletions, the magnitude of disease-related effects varied between donor lines. Towards mechanisms, FMRP targets and synaptic genes were overrepresented among dysregulated mRNAs and as such may contribute to the schizophrenia and epilepsy effects we observe. Further model validation, and new candidate epilepsy genes, comes from machine-learning analyses showing a striking similarity between a subset of dysregulated transcripts and well-established epilepsy genes. Results provide support for an important contribution of CYFIP1 in 15q11.2 mediated risk for NDDs and demonstrate that disease-related biological signatures are evident prior to neuronal differentiation. This new human model of disease will be useful in identifying compounds that could ameliorate outcomes in deletion carriers. Overall design: Investigation of CYFIP1 shRNA knockdown in three neural progenitor cell lines derived from induced pluripotent stem cells (3 control samples and 3 knockdown samples analyzed in each line)
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks.
No sample metadata fields
View SamplesWe expressed either only the E7 oncoprotein or the complete early genome region (CER) of the human papillomavirus type 8 in primary human adult skin keratinocytes.
Novel Insights Into Cellular Changes in HPV8-E7 Positive Keratinocytes: A Transcriptomic and Proteomic Analysis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View SamplesDendritic Cell differentiation - Transcription Regulator cluster follow-up: The data files associated to this experiment show gene expression levels for a subset of 481 transcripts (out of 12626 genes represented on Affymetrix Genechip HG_U95Av2) corresponding to Transcription Regulators whose expression is changed during the differentiation process of Dendritic Cells as assessed in the 9 conditions tested. Another subset of genes, corresponding to a cluster of CD molecules is available from E-MEXP-1 experiment.
Transcriptional profiling identifies Id2 function in dendritic cell development.
Sex, Specimen part, Time
View SamplesAnalysis of gene expression on day four and day six after tumor inoculation.
Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth.
Specimen part
View SamplesWithin the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View SamplesWithin the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View SamplesWe report a new unsupervised clustering tool for single cell RNA-seq data called SC3. We show that biologically relevant information can be obtained from preneoplastic cells of patients with myeloprolifertive disease. Overall design: examination of three different patients with myeloproloferative disease
SC3: consensus clustering of single-cell RNA-seq data.
No sample metadata fields
View SamplesPseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P. aeruginosa virulence in C. elegans. Approximately half of the hits were known antimicrobials. A large number of hits were non-antimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine anti-virulent compound, with no bacteriostatic or bacteriocidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P. aeruginosa.
A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.
Specimen part, Treatment
View Samples